In 1983, Brindley injected the corpora of several SCI men with phentolamine (85). Two out of the three men had a sufficient erection produced. Since then multiple reports on the efficacy of intracavernosal therapy have been published using, phentolamine, papaverine, prostaglandin, vasoactive intestinal peptide (VIP), and these medications in combination (86-90). These medications have been found to be extremely effective for neurogenic ED due to their ability act locally and essentially bypassing neuronal pathways. Local therapies are usually considered second-line after PDE5i fail to elicit a desired response which can occur in about 25–30% of men with ED, in general (91). Furthermore, the locally delivered medications can be quite dangerous if not used appropriately as priapism and significant pain with injections can occur. These specific occurrences have been suggested as a reason for high discontinuation rates with intracavernosal therapy (92).
In many cases, diagnosing erectile dysfunction requires little more than a physical exam and a review of your symptoms. If your doctor suspects that an underlying health problem may be at play, however, he may request additional testing. Once you’ve determined the cause for your ED, you and your doctor can decide on a form of treatment – here are some of the options:
The U.S. FDA (Food and Drug Administration) has a list of 29 OTC products that claim to treat erectile dysfunction. Patients should avoid these because many contain harmful ingredients. Other natural or herbal remedies such as DHEA, L-arginine, ginseng, and yohimbe are supplements that have been used but have not been proven safe and effective according to some researchers. Before using such compounds, individuals should consult their doctor. According to some experts, acupuncture does not effectively treat erectile dysfunction. Other home remedies for reducing ED symptoms include diet changes such as eating blueberries and citrus fruits and drinking red wine.
Centrally active compounds such as apomorphine have been used in men with ED whose cardiovascular comorbidity may prohibit PDE5i use, or in men who have concurrent apomorphine use for its anti-parkinsonian properties. Unfortunately, its side effect profile and poor effectiveness compared to other ED treatments have impaired its mainstream utilization (118). It is suspected that the side effects of apomorphine relate to its D2 receptor affinity. D4 receptor agonists, such as ABT-724 and azulenylmethylpiperazines, may not have the same associated side effects and show potent pro-erectile effects in animal models compared to apomorphine (32,119).

"Sexual relations are not only an important part of people's wellbeing. From a clinical point of view, the inability of some men to perform sexually can also be linked to a range of other health problems, many of which can be debilitating or potentially fatal," says Professor Gary Wittert, Head of the Discipline of Medicine at the University of Adelaide and Director of the University's Freemasons Foundation Centre for Men's Health.
Surgery: If neither drugs nor the vacuum pump works, your doctor may suggest surgery. With surgery, the doctor can place a device in your penis that will cause enough hardness for intercourse. In a few cases, infections may develop after the operation, and the doctor may have to remove the device. Another operation that may help you is rebuilding the blood vessels in the penis to increase blood flow into the penis or decrease blood flow out of the penis. These procedures can help you to get and maintain an erection.
Usually there will not be a specific treatment that will lead to the improvement of erectile dysfunction. However, there are treatments that will allow erections to happen and can be used to allow sexual activity to take place. There are three main types of treatments: non-invasive treatments such as tablet medicines and external devices (e.g. vacuum device); penile injections; or for men who have not had success with other treatments, surgery may be an option.
ED is often the result of atherosclerosis, and as a result, men with ED frequently have cardiovascular disease. Sexual activity is associated with increased physical exertion, which in some men may increase the risk of having a heart attack (myocardial infarction or MI). The major risk factors associated with cardiovascular disease are age, hypertension, diabetes mellitus, obesity, smoking, abnormal lipid/cholesterol levels in the blood, and lack of exercise. Individuals with three or more of these risk factors are at increased risk for a heart attack during sexual activity. The Princeton Consensus Panel developed guidelines for treating ED in men with cardiovascular disease. Thus, if you have ED and cardiovascular disease (for example, angina or prior heart attack), you should discuss whether or not treatment of ED and sexual activity are appropriate for you.
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Finally, gene therapy and stem cell research has widened the frontier of ED treatment proposed as possibility to even reverse ED. Specifically, gene therapy pertains to repairing the cause of ED by restoring defective gene function and/or altering the expression of the mutant gene (32). Most of the available data on gene therapy are in the animal model. However, a phase I clinical trial in men with ED undergoing intracavernous injection with a DNA plasmid carrying the alpha-subunit of the corporal smooth muscle Maxi-K channel showed promise in increased erectile function based on IIEF assessment sustained throughout the 3-month study period (122).


Erectile dysfunction (previously called impotence) is the inability to get or maintain an erection that is sufficient to ensure satisfactory sex for both partners. This problem can cause significant distress for couples. Fortunately more and more men of all ages are seeking help, and treatment for ED has advanced rapidly. The enormous demand for “anti-impotence” drugs suggests that erection problems may be more common than was previously thought. Find out more about the causes and treatment of erectile dysfunction here.
As with most other organ system in the human body, changes and loss of function is normal consequence of the ageing process. This is also true of the endocrine system, specifically the levels of testosterone production from the Leydig cells of the testicle. Accompanying the decrease in testosterone is a decrease in erections which also has a component in decrease in the blood supply to the penis making erection not as frequent and not as rigid compared with a young man’s erectile function. Although these changes are in itself not life threatening, they can impact a man’s relationship with his partner, and also ED may be a harbinger of other undiagnosed conditions such as coronary artery disease (CAD), hypercholesterolaemia or diabetes mellitus.6

Vascular damage may result from radiation therapy to the pelvis and prostate in the treatment of prostate cancer. [36] Both the blood vessels and the nerves to the penis may be affected. Radiation damage to the crura of the penis, which are highly susceptible to radiation damage, can induce ED. Data indicate that 50% of men undergoing radiation therapy lose erectile function within 5 years after completing therapy; fortunately, some respond to one of the PDE5 inhibitors.
Treatments include psychotherapy, adopting a healthy lifestyle, oral phosphodiesterase type V (PDE5) inhibitors (Viagra, Levitra, Cialis, Stendra, and Staxyn), intraurethral prostaglandin E1 (MUSE), intracavernosal injections (prostaglandin E1 [Caverject, Edex], Bimix and Trimix), vacuum devices, penile prosthesis and vascular surgery, and (in some cases) changes in medications when appropriate.
The role of the endothelium in ED has been noted for a number of years and the overlapping of ED and other conditions, especially coronary heart disease, CVD, affecting endothelial function/dysfunction, is clearly present. The endothelial cell is now known to affect vascular tone and impact the process of atherosclerosis, and impacting ED, CVD and peripheral vascular disease.16
ED is often the result of atherosclerosis, and as a result, men with ED frequently have cardiovascular disease. Sexual activity is associated with increased physical exertion, which in some men may increase the risk of having a heart attack (myocardial infarction or MI). The major risk factors associated with cardiovascular disease are age, hypertension, diabetes mellitus, obesity, smoking, abnormal lipid/cholesterol levels in the blood, and lack of exercise. Individuals with three or more of these risk factors are at increased risk for a heart attack during sexual activity. The Princeton Consensus Panel developed guidelines for treating ED in men with cardiovascular disease. Thus, if you have ED and cardiovascular disease (for example, angina or prior heart attack), you should discuss whether or not treatment of ED and sexual activity are appropriate for you.
Since the advent of PDE5i, many other selective and non-selective peripheral acting compounds have been developed or are in development. Avanafil has shown promising results in treating ED in post-prostatectomy patients with suspected cavernous nerve injury (111). Other PDE5i marked in Asia such as udenafil, and mirodenafil also effective at treating ED may minimize side effects due to shorter half-lives (112-114). Soluable guanylate-cyclase inhibitors and potassium channel activators are compounds that have induced erections in animal models but remain experimental requiring further investigation (115-117).
The main surgical treatment of ED involves insertion of a penile implant (also called penile prostheses). Because penile vascular surgery is not recommended for aging males who have failed oral PDE5 inhibitors, ICI or IU therapies, implants are the next step for these patients. Although placement of a penile implant is a surgery which carries risks, they have the highest rates of success and satisfaction among ED treatment options.
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